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01.
arXiv (quant-ph) 2026-06-12

Invariant Measures and Weak-Magic-Injection Asymptotics in Random Monitored Quantum Circuits

arXiv:2606.13470v1 Announce Type: new Abstract: Monitored quantum circuits provide a natural setting in which scrambling, measurements, and measurement-conditioned updates compete within a stochastic many-body dynamics. From the viewpoint of nonstabilizer resource theory, this competition is especially relevant because Clifford-compatible operations preserve the stabilizer structure, while weak non-Clifford perturbations inject magic resource. Most of the existing understanding of monitored quantum circuits has been shaped by numerical simulations and phenomenological descriptions, while a rigorous dynamics theory remains less developed. In this paper, we address this gap by developing an analytical framework which lays a rigorous mathematical foundation for the study of random monitored quantum dynamics. Specifically, we study a class of monitored quantum circuits driven by random Clifford. We prove the existence and uniqueness of the stationary law, which gives an ergodic description of the long-time dynamics. We then resolve the leading asymptotics of steady magic in the weak-magic-injection limit. This tangent description makes the contrast between resource measures transparent: in odd-prime local dimension, the steady Gross–Wigner mana has a linear leading asymptotic, whereas in qubit systems the steady 2-stabilizer Rényi entropy has a quadratic leading asymptotic. These different powers reflect the distinct local geometries of the two resource measures near the stabilizer layer. In this way, this work develops an analytical framework that first establishes the stationary ergodic dynamics of random monitored quantum circuits.

02.
arXiv (CS.LG) 2026-06-16

Localized Kernel Projection Outlyingness: A Two-Stage Approach for Multi-Modal Outlier Detection

arXiv:2510.24043v4 Announce Type: replace Abstract: This paper presents Two-Stage LKPLO, a novel multi-stage outlier detection framework that overcomes the coexisting limitations of conventional projection-based methods: their reliance on a fixed statistical metric and their assumption of a single data structure. Our framework uniquely synthesizes three key concepts: (1) a generalized loss-based outlyingness measure (PLO) that replaces the fixed metric with flexible, adaptive loss functions like our proposed SVM-like loss; (2) a global kernel PCA stage to linearize non-linear data structures; and (3) a subsequent local clustering stage to handle multi-modal distributions. Comprehensive 5-fold cross-validation experiments on 10 benchmark datasets, with automated hyperparameter optimization, demonstrate that Two-Stage LKPLO achieves state-of-the-art performance. It significantly outperforms strong baselines on datasets with challenging structures where existing methods fail, most notably on multi-cluster data (Optdigits) and complex, high-dimensional data (Arrhythmia). Furthermore, an ablation study empirically confirms that the synergistic combination of both the kernelization and localization stages is indispensable for its superior performance. This work contributes a powerful new tool for a significant class of outlier detection problems and underscores the importance of hybrid, multi-stage architectures.

03.
arXiv (CS.CV) 2026-06-16

AI for Maritime Security: Comparative Evaluation of CNN and Vision Transformer Architectures for Maritime Object Detection

This study aims to enhance maritime security by using advanced Artificial Intelligence (AI) and Computer Vision (CV) techniques. For this purpose, it was designed and assessed intelligent object detection systems that can detect the presence of ships on the sea surface under different real-time environments. To achieve this goal, a maritime image dataset with 6,468 images was used, covering different weather conditions like cloudy, foggy, rainy, and sunny environments. Six deep learning architectures were evaluated, including a base Convolutional Neural Network (CNN) model, four transfer learning models (Xception, VGG16, MobileNetV2, and EfficientNetV2L), and a Vision Transformer (ViT) model. The models were compared using multiple performance indicators, including accuracy, Type I and Type II errors, model size, and video processing time. The results show that model performance varies depending on computational constraints and deployment conditions. While lightweight architectures are suitable for resource-limited devices, the ViT achieved the best overall performance, reaching 100% accuracy with the lowest error rates and the fastest video processing time. The findings highlight the potential of AI-driven computer vision systems for maritime surveillance, border protection, and autonomous navigation.

04.
arXiv (CS.AI) 2026-06-15

A Fixed-Point Neural Operator for Size- and Functional-Transferable Hamiltonian Prediction

arXiv:2606.14498v1 Announce Type: cross Abstract: Predicting the Kohn-Sham Hamiltonian with machine learning can accelerate density functional theory while retaining access to molecular orbitals, energy levels, and electronic-structure observables that energy-only surrogates cannot resolve. Yet element-wise agreement with the converged Hamiltonian, an implicit fixed point of the self-consistent field iteration, does not determine the occupied subspace that governs orbital energies and densities. Here we present HamEvo, a neural operator that learns the single-step self-consistent update and returns the converged Hamiltonian as its fixed point. HamEvo is pre-trained on intermediate self-consistent trajectories and calibrated at equilibrium with density-matrix supervision. Across benchmarks from MD17 to drug-like QMugs, HamEvo lowers Hamiltonian errors by 35-49% over direct-regression and deep-equilibrium baselines, and predicts QMugs HOMO and LUMO energies with mean absolute errors of 0.036 and 0.053 eV, near the 1 kcal/mol chemical-accuracy scale. Few-shot fine-tuning with only 20 reference conformations extends HamEvo to molecules of up to 122 atoms, well beyond the size range covered by pre-training. With thermal molecular-dynamics sampling, HamEvo captures temperature-dependent HOMO-LUMO gap renormalization beyond the harmonic approximation. Inference is up to 242 times faster than conventional DFT.

05.
PLOS Computational Biology 2026-06-11

MicroRNA target gene prediction model based on input-feature dependency and sample data expansion technique

作者:

by Yan Shao, Yazhou Li, Hexin Zhai, Shimin Dong Predicting microRNA target genes is essential for understanding their biological functions. This study developed a miRNA target gene prediction model based on input-feature dependency. Features were treated as multiple random variables, with marginal densities estimated using Gaussian mixture models (GMM) and dependencies captured by regular vine (R-vine) copula to derive joint probability density functions. We constructed class-conditional joint densities for positive and negative samples separately using GMM and R-vine copula, then combined these with prior probabilities using Bayes’ rule to obtain posterior probabilities of positive interactions, using a standard 0.5 probability threshold for deterministic prediction. To address insufficient data and class imbalance, hybrid distribution mega-trend diffusion was used to generate virtual samples for data augmentation. Computational validation showed high predictive performance even when only 30% of the training data were used. As proof-of-concept, we experimentally validated one predicted interaction (miR-8485 targeting JAK2) using dual-luciferase, cellular, and animal experiments, confirming the biological relevance of this specific model-generated prediction. These findings provide a valuable tool for understanding miRNA functions and disease mechanisms.

06.
arXiv (CS.CL) 2026-06-11

When is Your LLM Steerable?

Activation steering offers a lightweight approach to control language models' behavior at inference time, but whether it succeeds or fails heavily depends on the prompt, concept, model, and steering configuration. Finding the regime and boundaries of successful steering typically requires expensive grid searches and post-hoc evaluation of full autoregressive rollouts. In this work, we investigate whether steerability can be predicted from the model's internal states at the beginning of the generation process, e.g., after generating the first few tokens, and how to leverage such a predictor to improve steering success rate. To this end, we first introduce ASTEER, a testbed including 1.4M steered generations, spanning 150 concepts with each steering success/failure labeled. Leveraging this testbed, we analyze the model's early decoding dynamics by extracting features that compare hidden states before and after steering across layers and initial decoding steps. These features help us understand how steering's effects propagate along layers and token positions, which provide key information for steerability prediction. We then train a Gradient Boosting Decision Trees (GBDT) classifier on these features to predict whether an intervention will under-steer, succeed, or over-steer without requiring full rollout. Our predictor achieves around 0.7 macro-F1 score on unseen concepts, demonstrating that early hidden states encode substantial, structured information about eventual steering efficacy. We further leverage this steerability predictor as guidance for steering strength searching, achieving near-optimal performance with a small fraction of decoding cost.

07.
arXiv (CS.CV) 2026-06-12

EquiDexFlow: Contact-Grounded SE(3)-Equivariant Dexterous Grasp Generative Flows

Most learned dexterous grasp generators relegate contact forces to a downstream verification step, so a kinematically-plausible pose can still violate the conditions for a stable physical grasp. We address this with EquiDexFlow, an SE(3)-equivariant flow-matching model that jointly predicts wrist pose, joint angles, fingertip contacts, surface normals, and contact forces from an object point cloud. Our architecture projects contacts onto the object surface and forces into the Coulomb friction cone by construction, so placement and friction compliance hold without loss penalties. We prove end-to-end SE(3) equivariance and verify it empirically over 200 rotations, with wrist residuals below $0.04^\circ$ and exactly zero joint deviation. Trained on 8,100 force-closure grasps across 81 objects for the 16-DoF Allegro Hand, our model achieves zero friction violations, the best composite score, and the lowest wrench residual among all ablation variants. We retarget decoded fingertip contacts to a 16-DoF LEAP Hand via per-finger inverse kinematics, and our hardware-feasible refinement places every joint at least 5% inside its actuator envelope while preserving wrench balance. On the physical robot, retargeted EquiDexFlow-decoded grasps complete open-loop pick-and-hold trials on all six test objects, with every asymmetric object succeeding at both the canonical pose and a $120^\circ$ co-rotation. Videos, code, and checkpoints are available at https://equidexflow.github.io.

08.
arXiv (CS.AI) 2026-06-17

Surrogate Assisted Pedestrian Protection Design via a Foundation Model Orchestrated Workflow

arXiv:2606.17577v1 Announce Type: new Abstract: AI-driven engineering workflows face particular challenges in crash safety design: unlike aerodynamics, crash events involve highly nonlinear contact dynamics, material nonlinearity, and discrete state transitions that are difficult to capture with data-driven surrogate models. To the best of our knowledge, we present the first foundation model–orchestrated workflow for crash safety design that enables surrogate-assisted exploration for pedestrian protection, reducing evaluation time from hours per CAE simulation to seconds. The workflow integrates four components: (1) a surrogate trained on CAE crash simulations to predict pedestrian leg injury metrics from design parameters, achieving an average $R^2=0.87$ and providing distribution-free conformal prediction intervals; (2) multiobjective evolutionary search (NSGA-II) to discover diverse feasible parameter sets under user-specified constraints; (3) a morphing-based geometry generator that maps parameters to topology-preserving 3D shapes; and (4) a natural-language interface in which an LLM orchestrates the workflow and a vision–language model supports semantic comparison of generated designs. In an automotive front-bumper case study, the workflow produces 35 distinct safety-compliant alternatives from a single exploration, a process that would require weeks with conventional CAE iteration. These results suggest that foundation models can serve as integration layers between ML surrogates and physics-based simulation, helping bring AI capabilities to safety-critical engineering domains.

09.
arXiv (CS.CV) 2026-06-11

Towards Fully Automated Exam Grading: Fairness-Aware Recognition of Handwritten Answers with Foundation Models

Correcting handwritten exams by hand is time-consuming and error-prone, particularly for large cohorts, while fully digital exams tend to force a didactic narrowing towards closed question formats. A practical middle ground keeps paper-based, problem-oriented tasks but records the assessment-relevant answers as single capital letters in a table that a machine can read. The open question is whether this reading can be made accurate and, above all, fair enough for unsupervised grading. Earlier automated approaches reached only about 88%–91% recognition – too low – and failed on the cases that matter most: answers placed outside the cell, crossed out, or written in cursive. We show that general-purpose vision-language foundation models (VLMs), which interpret the page rather than match pixel templates, close this gap. On a benchmark of 61 anonymised exams (3141 answer positions) the best model reaches 98.4% accuracy, well above the previous baseline. Crucially, we centre the evaluation on fairness: we distinguish false negatives (a correct answer marked wrong, which disadvantages the student) from false positives, and a lightweight prompt that supplies the reference solution as context lowers the false-negative rate to 0.58%. Under an exemplary grading scheme only three of the 61 exams would be graded worse, all caught by a student self-review step. Fully automated, fairness-aware exam grading at scale is therefore defensible; we release the anonymised benchmark to support reproducibility.

10.
arXiv (CS.LG) 2026-06-12

Optimal Spatio-Temporal Decoupling for Bayesian Conformal Prediction

arXiv:2605.00432v2 Announce Type: replace Abstract: Online conformal prediction must balance fast adaptation to distribution shift against stable coverage: feedback-driven methods react quickly but become volatile, while strongly discounted Bayesian methods lag and inflate intervals at tight coverage. We introduce State-Adaptive Bayesian Conformal Prediction (SA-BCP), which forms the predictive quantile as a gated convex combination of long-term temporal inertia and local spatial evidence from a kernel density estimate, controlled by a single interpretable evidence threshold $K$. We establish three results: (i) asymptotic marginal validity of the resulting intervals; (ii) a closed-form expression for the MSE-optimal threshold, $K^*_{\mathrm{MSE}}=\alpha(1-\alpha)/M^{\mathcal{T}}$, trading the coverage-indicator (Bernoulli) variance against the temporal structural bias $M^{\mathcal{T}}$; and (iii) a rolling-origin procedure for selecting $K$ online – consistent under stationarity, with $O(\sqrt{T\log N})$ regret against the best fixed $K$ and, for a segmented variant, a sublinear dynamic-regret bound under bounded drift. Across four financial-volatility and weather datasets, three target coverage levels, and eight baselines (including the strongest recent conditional-quantile methods, SPCI and KOWCPI), SA-BCP attains at-or-above-nominal coverage in most settings while producing substantially sharper intervals – up to roughly $3\times$ lower Winkler score than discounted Bayesian CP at the tightest coverage – and a coverage-matched audit confirms these efficiency gains are not an artifact of under-coverage. We disclose one principal limitation: a volatility-specialized conformal-GARCH competitor remains more efficient on its home volatility-base series, though it does not transfer across domains.

11.
Nature Medicine 2026-06-15

Activity-dependent adaptive deep brain stimulation improves gait in Parkinson’s disease

Parkinson’s disease leads to a spectrum of locomotor deficits that vary in severity with the nature of daily activities and the fluctuating physiology of patients. Many of these deficits remain inadequately addressed by existing deep brain stimulation therapies that rely on activity-agnostic parameters optimized for cardinal motor symptoms. By contrast, therapies embedding activity-specific parameters have the potential to better address the entire range of symptoms. Here we expose physiological principles that enable real-time decoding of ongoing locomotor activities across motor fluctuations from the neural dynamics of the subthalamic nucleus. This decoding steered activity-dependent adaptations of deep brain stimulation therapies that improved locomotor deficits while preserving efficacy for cardinal motor symptoms across activities of daily living. Our activity-dependent framework provides a blueprint for next-generation neuromodulation therapies that continuously select parameters optimized to the behavioral context and fluctuating physiology of each patient. ClinicalTrials.gov registration NCT06791902 . Neural decoding algorithms that leverage physiological principles of locomotor encoding support activity-dependent deep brain stimulation therapies that improve locomotor deficits in people with Parkinson’s disease.

12.
arXiv (CS.CV) 2026-06-17

MeiBRD: Meta-Learning Intraoperative Biomechanical Residual Deformation

Accurate intraoperative liver registration is challenging due to substantial soft-tissue deformation yet sparse intraoperative measurements. Biomechanical models regularize this ill-posedness with prior knowledge but exhibit persistent prediction bias due to simplifying assumptions, while data-driven learning solutions struggle with data efficiency, generalization, and physical plausibility. We propose a hybrid registration framework that adapts a biomechanical prior using sparse intraoperative correspondences. Rather than learning a full deformation field, we learn a residual deformation function that corrects linear biomechanical predictions, modeled as a graph neural diffusion function with geometry-aware attention over the 3D liver mesh. To enable long-range information transfer of sparse observations, we take a novel perspective of sparse intraoperative measurements as context samples where input-output pairs of the residual deformation function are fully observed, casting the problem into learning-to-learn this residual function from intraoperative context samples with feedforward meta-learners. Experiments on a deformable liver phantom dataset demonstrate improved registration accuracy and generalization compared to rigid, biomechanical, and data-driven baselines, particularly for out-of-distribution geometries and deformations.

13.
arXiv (CS.CV) 2026-06-16

MNet++: Extended 2D/3D Networks for Anisotropic Medical Image Segmentation

This work demonstrates a full reproduction and extension of MNet, a hybrid 2D/3D convolutional network designed for anisotropic medical image segmentation. The original architecture was re-implemented within the nnU-Net framework to verify its reported performance and robustness to variable voxel spacing, known as anisotropy. Experiments were conducted on PROMISE prostate MRI and a controlled subset of LiTS liver CT under matched preprocessing and compute constraints. The reproduced MNet achieved a Dice similarity coefficient (DSC) of 89.0 +/- 0.9% on PROMISE, within 0.8% of the published result, and 94.3 +/- 1.9% / 54.6 +/- 3.1% for liver and tumor segmentation on LiTS, respectively. Two lightweight extensions were further introduced: (1) a learned Fusion Gating mechanism enabling adaptive 2D-3D feature blending, and (2) a VMamba state-space module for efficient long-range depth modelling. The Spatial Gating variant improved DSC by +0.8% with less than 3% inference overhead, while VMamba improved performance consistency, reducing PROMISE Dice variation to +/- 0.7% and achieving the strongest LiTS liver performance at 95.8% Dice. Both extensions preserved MNet robustness to anisotropy, with delta Dice = 1.5% across 1-4 mm voxel spacing. Overall, the study confirms MNet reproducibility and demonstrates that adaptive fusion and state-space modelling have the potential to further strengthen segmentation reliability under anisotropic conditions. However, further tests are required to provide definitive conclusions.

14.
arXiv (CS.CL) 2026-06-15

"I Didn't Make the Micro Decisions": Measuring, Inducing, and Exposing Goal-Level AI Contributions in Collaboration

As large language models (LLMs) increasingly shape how users form, refine, and extend their goals, attributing contributions in human-AI collaboration becomes critical for users calibrating their own reliance and for evaluators assessing AI-assisted work. Yet existing methods focus on final artifacts, missing the process through which goals themselves are jointly shaped. We introduce a goal-level attribution framework, CoTrace, that decomposes explicit goals into verifiable requirements and traces both direct contributions and indirect influences across dialogue turns. Applying CoTrace to 638 real-world collaboration logs, we find that while models account for only 11-26% of goal-shaping contribution, they contribute substantially more on introducing lower-level concrete requirements, and make various kinds of indirect contributions. Through controlled simulations, we show that interaction design choices significantly affect model goal-shaping behavior. In a user study, exposing participants to goal-level analyses shifts their perceived contributions by nearly 2 points on a 5-point scale, revealing systematic miscalibration in how users understand their own AI-assisted work.

15.
arXiv (CS.CV) 2026-06-16

Avoiding Exponential Blow-Up in Distributive Lattice Submodular Minimization

作者:

Submodular function minimization has gained a lot of interest in recent years. They are highly applicable in the area of Computer Vision and Machine Learning. Often such applications require to work with submodular functions defined on distributive lattice. Current best way of dealing with it is using a transformation which extrapolates the submodular function for the respective boolean lattice. It makes optimization system too inefficient due to enlargement of the working space. Quantitatively, the expanded space has additional exponential (in set size) number of elements. We propose a generic framework for dealing with distributive lattice which only works within distributive lattice. Our framework allows one to use already established submodular function minimization algorithms for boolean lattice. In our experiment, we show the huge improvement in terms of running time over tranditional methods for handling distributive lattice.

16.
Nature (Science) 2026-06-22

Stereoretentive decarbonylative C(sp<sup>3</sup>)-C(sp<sup>3</sup>) cross-coupling

作者:

While C(sp3)–C(sp3) bond-forming cross-coupling methods have become more common, stereocontrolled bond-formation remains a challenge,1 despite its importance for drug discovery, where there is a emerging demand for molecules with increased sp3 character.2-4 Enantiospecific cross-coupling approaches would complement advances in enantioselective coupling,5-8 but have been limited to specialized substrates with lower availability5,9 because stereospecific oxidative addition of more abundant chiral alkyl electrophiles is unknown.10 Inspired by the classic, stereoretentive Curtius rearrangement,11 herein we disclose a catalytic strategy that proceeds by an analogous stereoretentive decarbonylation step to form a versatile chiral alkylnickel intermediate from easily-available chiral amino-acid and α-hydroxy-acid derivatives. The chiral alkylnickel intermediates decompose and/or racemize on the order of minutes, but are sufficiently stable to enable stereoretentive cross-electrophile coupling12 with alkyl radicals (derived from alkyl iodides) at relatively low temperature (22-40 °C). This mechanistic strategy provides a straightforward approach to stereocontrolled C(sp3)–C(sp3) bond formation, including diastereomers that are inaccessible by stereoselective radical mechanisms. The “metallo-Curtius” strategy described in this study lays a mechanistic foundation for the development many new stereospecific cross-coupling reactions.

17.
medRxiv (Medicine) 2026-06-15

Midwifery Practice in Conflict Contexts: Lived Experiences from Somalia and Nigeria

Background: Midwives are a central cadre in the health system, particularly in conflict-affected settings where they are sometimes the primary or even only skilled providers available. Yet, despite their critical role, there is limited qualitative evidence capturing their lived experiences and how these shape workforce entry, retention, and overall well-being. Methods: Drawing on a phenomenological research methodology, this qualitative study was embedded within a larger prospective longitudinal cohort of midwifery students and graduates in Somalia and Nigeria. We conducted focus group discussions with graduate midwives (n=48 in Nigeria; n=63 in Somalia) to explore their experiences transitioning into the workforce and their realities working in health systems impacted by conflict and violent insecurity. Data were analysed using inductive thematic analysis. Results: Five themes emerged from the data: (1) job search and workforce entry, which was described as fraught with challenges and shaped by a set of formal systems in Nigeria but informal networks and structural barriers in Somalia (2) working conditions that were marked by resource scarcity, infrastructural challenges, and heavy and unreasonable workloads, (3) safety, security and coping strategies that differed across the two contexts but reflected persistent exposure to violence and a reliance on ad hoc and personal coping in lieu of systematic protection, (4) community perceptions of midwives, shaped and constrained by social and gender norms and (5) mental health and emotional wellbeing, highlighting stress, burnout and moral injury experienced by this cadre. Conclusion: Our findings highlight the profound challenges faced by midwives working in conflict-affected settings, and they shine a light on the urgent need to support and invest in this critical and predominantly female health workforce.

18.
arXiv (CS.LG) 2026-06-17

Accelerated Convex Optimization via Hamiltonian Dynamics with Deterministic Integration Time

arXiv:2606.17260v1 Announce Type: cross Abstract: We develop Hamiltonian dynamics-based algorithms for smooth convex optimization that achieve accelerated rates of convergence. By exploiting contraction of averaged Hamiltonian flow trajectories rather than requiring contraction at trajectory endpoints, we show that Hamiltonian dynamics-based optimization methods admit deterministic and accelerated convergence guarantees, extending prior work that is limited to quadratic objectives or holds only in expectation. We analyze an idealized continuous-time algorithm and derive practical discrete-time implementations with optimal first-order complexity, thereby establishing Hamiltonian dynamics as a useful algorithmic primitive for deterministic accelerated convex optimization.

19.
arXiv (CS.AI) 2026-06-12

A Quantitative Experimental Repeated Measures Study of Training Dynamics in a Small Llama Style Language Model Under a Compute-Aware Token Budget

作者:

arXiv:2606.13370v1 Announce Type: new Abstract: This study examines training dynamics in a small Llama-style language model trained under a fixed, compute-constrained token budget. Rather than evaluating efficiency solely through endpoint performance, the study uses a quantitative experimental repeated measures design to analyze how validation loss, validation perplexity, rolling volatility, backslide behavior, spike behavior, and between-seed variability change across token-based training intervals. Six independent training runs were conducted on a 4.26-million-parameter model using the TinyStories corpus, CPU-based full-precision training, and a target budget of approximately 20 million cumulative training tokens. Metrics were collected across 21 intervals, producing 126 seed-by-interval observations. Repeated measures ANOVA showed statistically significant interval effects for validation loss, validation perplexity, and rolling volatility. Descriptive trajectories revealed rapid early improvement followed by non-monotonic degradation during later training intervals. Mean validation loss decreased from 8.3552 at initialization to 2.7996 near 4 million tokens, but increased to 3.9010 by the final checkpoint. Validation perplexity followed the same pattern, falling sharply early in training before rising later. Derived telemetry further showed recurrent validation-loss backslides and no interval-summary evidence of a stable phase under the predefined criteria. These findings suggest that compute-aware language model evaluation should examine training trajectories rather than endpoint metrics alone. In constrained compute settings, additional token exposure may increase computational cost without producing proportional generalization gains, and interval-level telemetry can reveal instability, regression, and diminishing returns that final metrics may obscure.

20.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

21.
arXiv (CS.LG) 2026-06-16

A Fully First-Order Layer for Differentiable Optimization

arXiv:2512.02494v2 Announce Type: replace Abstract: Differentiable optimization layers enable learning systems to make decisions by solving embedded optimization problems. However, computing gradients via implicit differentiation requires solving a linear system with Hessian terms, which is both compute- and memory-intensive. To address this challenge, we propose a novel algorithm that computes the gradient using only first-order information. The key insight is to rewrite the differentiable optimization as a bilevel optimization problem and leverage recent advances in bilevel methods. Specifically, we introduce an active-set Lagrangian hypergradient oracle that avoids Hessian evaluations and provides finite-time, non-asymptotic approximation guarantees. We show that an approximate hypergradient can be computed using only first-order information in $\tilde{O}(1)$ time, leading to an overall complexity of $\tilde{O}(\delta^{-1}\epsilon^{-3})$ for constrained bilevel optimization, which matches the best known rate for non-smooth non-convex optimization. Furthermore, we release an open-source Python library that can be easily adapted from existing solvers. The source code is available at https://github.com/guaguakai/FFOLayer.

22.
arXiv (math.PR) 2026-06-11

Construction of ergodic IDLA forests in $\mathbb{Z}^d$

arXiv:2506.10476v2 Announce Type: replace Abstract: We prove the existence of infinite-volume IDLA forests in $\mathbb{Z}^d$ , with $d \geq 2$, based on a multi-source IDLA protocol. Unlike IDLA aggregates, the laws of the IDLA forests studied here depend on the trajectories of particles, and then do not satisfy the famous Abelian property. Their existence is due to a stabilization result (Theorem 1.1, our main result) that we establish using percolation tools. Although the sources are infinitely many, we also prove that each of them play the same role in the building procedure, which results in an ergodicity property for the IDLA forests (Theorem 1.2).

23.
arXiv (CS.AI) 2026-06-16

A Multi-Level Architecture for Reusable Materials Ontologies – The OntoCrafter Ceramics Ontology (OCO) as Reference Implementation

arXiv:2606.14814v1 Announce Type: cross Abstract: The Materials Science and Engineering ontology landscape is fragmented along multiple axes simultaneously. Horizontally: a recent survey identified 94 ontologies of which over 40 are structurally incompatible; each new application domain – ceramics, polymers, batteries, smart materials – typically restarts ontology design from scratch. Vertically: EU regulation (CSRD, CSDDD, PPWR, CBAM, R2R, AI Act, ESPR) forces material, manufacturing, supply-chain, and lifecycle data into integrated digital product passports, leaving ontologies that only address horizontal fragmentation incomplete for any contemporary consumer. And mechanistically: a vocabulary that records that BNT-BT has $d_{33} \approx 580$ pC/N stores a fact but cannot surface why – Bi-6s$^2$ lone-pair stereo-activity, anomalous Born effective charges, soft modes, defect chemistry – without a systematic explanation skeleton. We propose a multi-level modular architecture with two independent classification axes – level of abstraction (L0 bridges, L1 material-agnostic laboratory-notebook, L2 material-class-specific, L3 categorical reasoning) and consumer audience (material vs. compliance) – in which the material-specific level is internally organised by a seven-tier mechanistic-explanation skeleton (Symmetry, Energy/DFT, Thermo/CALPHAD, Kinetics, Microstructure, Defect chemistry, Bonding) applicable to any crystalline ionic oxide. The level-and-audience modularity dissolves the horizontal fragmentation, the compliance audience absorbs the vertical regulation pressure, and the seven-tier organisation of Level 2 delivers the mechanistic explanation depth. We instantiate the architecture as the OntoCrafter Ceramics Ontology (OCO v0.94): 5,196 classes across 44 modules; 167,348 OWL axioms (40,454 logical); 1,674 properties; 829 cross-ontology bridge mappings; 1,172 SHACL shapes; 163 published competency questions.

24.
arXiv (CS.LG) 2026-06-17

Learning and Generating Mixed States Prepared by Shallow Channel Circuits

arXiv:2604.01197v4 Announce Type: replace-cross Abstract: Learning quantum states from measurement data is a central problem in quantum information and computational complexity. In this work, we study the problem of learning to generate mixed states on a finite-dimensional lattice. Motivated by recent developments in mixed state phases of matter, we focus on arbitrary states in the trivial phase. A state belongs to the trivial phase if there exists a shallow preparation channel circuit under which local reversibility is preserved throughout the preparation. We prove that any mixed state in this class can be efficiently learned from measurement access alone. Specifically, given copies of an unknown trivial phase mixed state, our algorithm outputs a shallow local channel circuit that approximately generates this state in trace distance. The sample complexity and runtime are polynomial (or quasi-polynomial) in the number of qubits, assuming constant (or polylogarithmic) circuit depth and gate locality. Importantly, the learner is not given the original preparation circuit and relies only on its existence. Our results provide a structural foundation for quantum generative models based on shallow channel circuits. In the classical limit, our framework also inspires an efficient algorithm for classical diffusion models using only a polynomial overhead of training and generation.

25.
arXiv (quant-ph) 2026-06-17

Canonical regularization of the stationary Coulomb problem and an Aufbau-like spectral ordering

arXiv:2606.17359v1 Announce Type: new Abstract: The stationary hydrogen atom has Coulomb degeneracy across orbital levels, whereas the Aufbau/Madelung ordering is an empirical, many-electron rule established in atomic physics. We examine the hydrogen atom through a regularized de Broglie–Bohm representation, in which stationary amplitude current constraints generate separable Sturm–Liouville branches. In this formulation, the radial, orbital, and magnetic sectors acquire canonical Langer-like inverse square corrections. The modified boundary value problems allow analytical solutions and produce a hydrogen-like spectrum with regularized radial and angular indices. Consequently, radial Coulomb quantization acquires an orbital dependent shift, lifting the Coulomb degeneracy and producing a spectral ordering that follows the Aufbau/Madelung sequence. On this basis, we construct the ordering of the regularized de Broglie–Bohm states and show that the spectral structure retains the standard degenerate Rydberg sequence in the l=0 sector. The separated amplitudes are represented by generalized special function branches, including the associated Laguerre, Legendre, and Bessel functions with non-integral parameters arising from regularized separation. Therefore, the treatment is intended as an analytical examination of spectral ordering in a regularized one center Coulomb problem rather than as a replacement for the many electron atomic structure theory. Keywords: de Broglie–Bohm representation; Coulomb spectrum; canonical regularization; Langer correction; Sturm–Liouville equations; Aufbau principle; Madelung ordering; associated Legendre functions; associated Laguerre functions; Bessel functions.